Delivering Adenosine to a Bone Injury Accelerates Regeneration
A very large number of tissue-specific signals are involved in the mechanisms of regeneration, an intricate dance between many different cell types. It has long been the goal of the research community to identify the most important signals in this enormous repertoire and amplify them in a targeted way in order to enhance regeneration from injury or reverse age-related loss of tissue maintenance capacity. The work here is an example of the former goal, in which researchers find that adenosine can be delivered to bone injuries in a targeted way in order to accelerate healing.
Researchers have found that the body naturally floods the area around a new bone injury with the pro-healing adenosine molecules, but those locally high levels are quickly metabolized and don't last long. They wondered if maintaining those high levels for longer would help the healing process. But there was a catch. "Adenosine is ubiquitous throughout the body in low levels and performs many important functions that have nothing to do with bone healing. To avoid unwanted side effects, we had to find a way to keep the adenosine localized to the damaged tissue and at appropriate levels."
The solution was to let the body dictate the levels of adenosine while helping the biochemical stick around the injury a little bit longer. The researchers designed a biomaterial bandage applied directly to the broken bone that contains boronate molecules that grab onto the adenosine. However, the bonds between the molecules do not last forever, which allows a slow release of adenosine from the bandage without accumulating elsewhere in the body. Researchers first demonstrated that porous biomaterials incorporated with boronates were capable of capturing the local surge of adenosine following an injury. The researchers then applied bandages primed to capture the host's own adenosine or bandages preloaded with adenosine to tibia fractures in mice. After more than a week, the mice treated with both types of bandages were healing faster than those with bandages not primed to capture adenosine. After three weeks, while all mice in the study showed healing, those treated with either kind of adenosine-laced bandage showed better bone formation, higher bone volume, and better vascularization.
The results showed that not only do the adenosine-trapping bandages promote healing, they work whether they're trapping native adenosine or are artificially loaded with it, which has important implications in treating bone fractures associated with aging and osteoporosis. "Our previous work has shown that patients with osteoporosis don't produce adenosine when their bones break. These early results indicate that these bandages could help deliver the needed adenosine to repair their injuries while avoiding potential side effects."